Dr. McFadden will be joining the faculty as an Assistant Professor in the Department of Psychiatry at the University of Colorado School of Medicine. Her long-term research goal is to develop an independent program of research focused on identifying neuronal mechanisms underlying obesity and understanding how these effects interact with cognitive and metabolic factors to influence obesity, feeding behaviors, and successful weight maintenance. The proposed research is designed to facilitate her training to reach this goal. During the award period, training will focus on the short-term objectives of acquiring expertise in the neurobiology of obesity, fMRI methodology, energy balance, food intake behaviors, and weight loss interventions to reach the long-term objective of becoming an independent investigator in the field of obesity neurobiology. Obesity is a significant public health concern associated with an overall increased risk of mortality and risk of coronary heart disease and hypertension. Weight loss in obese individuals is associated with a reduction in these comorbid conditions. However, weight loss can be difficult, and preventing subsequent weight regain is even more challenging. Understanding the mechanisms underlying adaptations involved in regulating energy balance could help to identify strategies for successful weight-loss maintenance. The use of neuroimaging techniques such as functional magnetic resonance imaging (fMRI) allows the identification of neuronal pathways and networks associated with these signals in obesity and weight loss, providing insight into the central regulation of energy balance. Furthermore, the identification of sensitive neuronal measures that predict fat mass loss could provide a potential biomarker for therapeutic development. Cognitive inhibition and impulsivity during decision-making are important components of eating behaviors, critical for balancing immediate rewards (e.g., eating a desired, but high calorie food) with long-term goals (e.g., maintaining a healthy weight). High impulsivity and low inhibitory control may lead to overeating, contributing to weight gain and obesity. Identifying effective methods to improve neuronal function associated with cognitive control could be particularly useful for weight management. An attractive candidate for this is exercise. In addition to conferring physiological benefits, exercise may also alter neuronal function and related cognitive processes involved in eating behaviors, which can contribute to weight loss. The overall goals of the proposed research project are to determine how exercise affects neuronal function in obese individuals, and how this contributes to eating behaviors. To achieve these goals, neuronal responses and measures of eating behavior will be assessed before and after a 12-week exercise intervention, as compared to a diet intervention designed to elicit a similar deficit in energy balance. The proposed project will measure effects of exercise on the following: (1) neuronal response (insula and medial orbitofrontal cortex) during a cognitive control task, (2) neuronal activity in intrinsi resting state networks (default and salience networks), (3) ad libitum food intake and corresponding appetite measures, and (4) eating-related behaviors (food cravings, food-related reward, dietary restraint, dietary disinhibition). This study will contribute to the knowledge of te effects of exercise on neuronal function. This is significant because understanding the neuronal mechanisms underlying the effects of exercise on cognitive factors involved in eating behaviors will be helpful in the development of effective therapeutic strategies for weight loss and weight gain prevention. Dr. McFadden has a strong background in clinical neuroscience, intervention research in clinical populations, and neuroimaging (EEG/MEG), which makes her well-suited to complete the proposed research and training. However, she is new to the field of obesity and has recently begun training in obesity neurobiology and fMRI, so additional training will be necessary for her transition to independence. The combination of her expert mentor/consultant team and the excellent resources for brain imaging and obesity/metabolic research at the Anschutz Medical Campus (AMC) will support the development of her independent research career. In addition to training with her mentor/consultant team, Dr. McFadden will complete coursework in neuroscience, fMRI methodology, and exercise physiology to facilitate her training. The Anschutz Health and Wellness Center and other internationally recognized obesity/metabolic research resources at AMC are exceptional assets for Dr. McFadden's training and research, with the requisite facilities and intellectual resources for obesity, exercie and nutrition research. Dr. McFadden will also participate in a multitude of professional development activities to promote her transition to independence. The Colorado Clinical and Translational Sciences Institute (CCTSI) at AMC is an excellent NIH-funded resource for these career development opportunities. Completion of the proposed research and training goals will place Dr. McFadden in a strong position to develop an independent research program utilizing neuroimaging techniques to investigate neuronal mechanisms in obesity and weight loss.